tbuckley/cabot-search huggingface dataset:
CONTINUUM: A pilot care transition intervention for hospitalized patients with advanced cancer.
Authors: Daniel E Lage, Alane Schmelkin, Julia Cohn, Laurie Miller, Caroline Kuhlman, Elizabeth A. Krueger, Kara Marie Olivier, Dana Haggett, Christine Ritchie, Joseph A. Greer, Areej El-Jawahri, Ryan David Nipp, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2022)

1534 Background: Patients with advanced cancer are frequently hospitalized and experience burdensome transitions of care after discharge. Interventions to address patients’ symptoms, support medication management, and ensure continuity of care after discharge are lacking. We sought to demonstrate the feasibility and acceptability of CONTINUUM (CONTINUity of care Under Management by video visits) for this population. Methods: We conducted a single-arm pilot trial (n = 54) of CONTINUUM at Massachusetts General Hospital (MGH). The intervention consisted of a video visit with an oncology nurse practitioner (NP) within 3 business days of hospital discharge to address symptoms, medication management, hospitalization-related issues, and care coordination. Prior to discharge, we enrolled English-speaking adults with advanced breast, gastrointestinal, genitourinary, or thoracic cancers experiencing an unplanned hospitalization who were receiving ongoing oncology care at MGH and being discharged home without hospice services. We defined the intervention as feasible if ≥70% of approached and eligible patients enrolled and if ≥70% of enrolled patients completed the intervention within 3 business days of discharge. At 2 weeks after discharge, patients rated the ease of use of the video technology and stated whether they would recommend the intervention. NPs completed post-intervention surveys to assess fidelity to the intervention protocol. Results: From 01/07/21 to 05/28/21, we enrolled 54 patients (77.3% of patients approached). Of the enrolled patients (median age = 65.0 years; 59.3% and 22.2% had advanced gastrointestinal or thoracic cancers, respectively), 83.3% of enrolled patients received the intervention within 3 business days of discharge. Patient rating of the ease of use of video technology was a mean of 7.8 out of 10, with 71.4% stating they “agreed” or “strongly agreed” that they would recommend the intervention. NP post-intervention surveys revealed that visits focused on symptom management (85.7%), followed by addressing post-hospital care issues (69.0%). At 30 day follow up, 38.8% were readmitted within 30 days of discharge, and 12.2% died within 30 days of discharge. Conclusions: We found that CONTINUUM, which consists of an NP-delivered video visit soon after hospital discharge addressing patients’ symptoms, medications, and care coordination, represents a feasible and acceptable approach to provide post-discharge care for hospitalized patients with advanced cancer. Future studies will test the efficacy of the intervention for reducing hospital readmissions. Clinical trial information: NCT04640714.
Resistance to targeted therapies: delving into FLT3 and IDH
Authors: Sai Prasad Desikan, Naval Daver, Courtney DiNardo, Tapan Kadia, Marina Konopleva, Farhad Ravandi
Journal: Blood Cancer Journal (2022)

Recent advances in FLT3 and IDH targeted inhibition have improved response rates and overall survival in patients with mutations affecting these respective proteins. Despite this success, resistance mechanisms have arisen including mutations that disrupt inhibitor-target interaction, mutations impacting alternate pathways, and changes in the microenvironment. Here we review the role of these proteins in leukemogenesis, their respective inhibitors, mechanisms of resistance, and briefly ongoing studies aimed at overcoming resistance.
Addition of anti-PD1 antibodies to chemotherapy (CT) in first-line treatment of advanced esophageal cancer (EC): A systematic review and meta-analysis.
Authors: Anastasia Rice, Mikhail Fedyanin, Ekaterina Ignatova, Elizaveta Polyanskaya, Elmira Dinaeva, Natalia Besova, Alexey Tryakin
Journal: Journal of Clinical Oncology (2022)

e16055 Background: The addition of anti-PD-1 antibodies to first-line CT is the new standard of care for pts with advanced EC. However, available data on the efficacy of such therapy in different clinical subgroups is still lacking. Therefore, we performed a meta-analysis to determine the efficacy of combination anti-PD1 and systemic CT in terms of overall survival (OS) in pts with advanced EC. Methods: We searched PubMed, proceedings of ASCO, and ESMO conferences up to February 2022. We included prospective randomized phase III trials comparing the combination of anti-PD1 and CT with CT alone as the first-line treatment option for pts with advanced EC. The primary outcome was OS. Meta-analysis was conducted by Review Manager (Ver. 5.3) software. Results: Five trials with a total of 3163 pts were included, of which 1576 received anti-PD1+CT and 1587 received CT alone. There was a significant improvement in PFS (HR, 0.62; 95% CI, 0.56-0.67; p &lt; 0.00001; I 2 = 45%, p for heterogeneity 0.12), OS (HR, 0.69; 95% CI, 0.63-0.76; p &lt; 0.00001; I 2 = 0%) and ORR (OR, 2.07; 95% CI, 1.76-2.43; p &lt; 0.00001; I 2 = 21%) in pts received anti-PD1+CT. OS was improved in pts regardless of age, race, CT regimen, presence of liver metastases, ECOG PS, or histology. Subgroup analysis suggested that the addition of anti-PD1 have a better effect in pts with PDL expression on tumor cells &gt; 1, ≥ 10, and &lt; 10 and in pts with CPS ≥ 10, but not in pts with PDL &lt; 1. We found a tendency towards survival advantage in pts with CPS &lt; 10. No survival benefit was observed in women (tab). Conclusions: Improved OS was found to be associated with addition of anti-PD1 antibodies to systemic CT in different patient subgroups with advanced EC, except for female and in pts with low PDL expression. Despite of meta-analysis results we need prospective randomized trial for pts with CPS &lt; 10.[Table: see text]
Incorporating mediation-based interventions at an academic cancer center: A six-step process.
Authors: Neha M Jain, Emma Schremp, Lucy Spalluto, Travis John Osterman, Debra L. Friedman
Journal: Journal of Clinical Oncology (2022)

e18662 Background: A growing body of evidence, including NCCN guidelines for distress management in oncology, supports the use of meditation-based interventions (MBI) in cancer care. However, MBI are generally delivered outside of the cancer treatment setting, with no integration between meditation instructors and the oncology care team. Further, there have been no studies to evaluate implementation of this evidence-based practice into routine cancer care. We report on the implementation process for establishing an integrated MBI program at an NCI-designated comprehensive cancer center. Methods: Guided by the Consolidated Framework for Implementation Research (CFIR), we developed a discrete MBI program as a strategy to implement MBI in our cancer center. Program components included 1) identifying champions and key stakeholders; 2) engaging with patient navigators and patient advocates; 3) partnering with cancer center leadership to gain infrastructure support; 4) establishing a meditation-focused program to increase acceptability amongst providers and patients; 5) launching an IRB-approved study to measure study outcomes; 6) leveraging social media, patient newsletters, and other institutional communication modes to increase awareness. We used the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework to define the outcome measures including reach (number of patients who attended an MBI session), adoption (number of providers who referred patients to MBI and number of patients who attended &gt; 1 MBI session), and implementation (feasibility and acceptability). Results: An MBI program has been successfully established within an NCI-designated comprehensive cancer and has received enthusiastic support from oncology providers, research nurses, as well as patient advocate groups. The intervention is delivered three times a week in 30 min sessions via videoconferencing. At the end of each session patients are encouraged to complete a short online survey about their experience. The first class has been established and enrolment is ongoing. Conclusions: Given the high prevalence of psychosocial distress in a rapidly expanding global cancer population, implementation of strategies to integrate psychosocial interventions, such as meditation, into routine care is critical. Well-defined MBI programs such as this can overcome the misperception that MBIs are difficult to implement in cancer centers and support the successful implementation of MBIs within cancer programs. Adoption of this evidence-based strategy can positively impact patient psychological resilience.
Cascade testing of first-degree relatives of patients with pancreatic cancer with confirmed germline genetic mutations: A simulation modeling study.
Authors: Mary Linton Bounetheau Peters, Barak Davidi, Claudia L. Seguin, Andrew Eckel, Pari Pandharipande
Journal: Journal of Clinical Oncology (2022)

10513 Background: Universal germline genetic testing is recommended for all patients with pancreatic ductal adenocarcinoma (PDAC). In addition to treatment implications for the patient, it is valuable for family members of the PDAC patient to undertake germline testing to understand their familial cancer risk. We evaluated the potential effectiveness of cascade testing of first-degree relatives (FDRs) of PDAC patients to guide MRI-based screening for PDAC. Methods: We used a microsimulation model of PDAC to estimate the potential life expectancy (LE) benefit of cascade genetic testing of FDRs of PDAC patients. Analysis was performed for eight mutations of interest (ATM, BRCA1, BRCA2, PALB2, Lynch, TP53, CDKN2A, STK11) with relative risk of PDAC ranging from 1.6 – 24. FDRs were defined by their sex, age, and information state (not informed, informed but not tested, test negative, or test positive). Family size and composition, communication of genetic testing results, and uptake of cascade testing were based on published studies. For each FDR group, we simulated multiple MRI-based screening strategies, defined by starting age (FDR age at patient diagnosis to age 75) and frequency (once or annual until age 75), and identified the strategy that resulted in the highest LE. Results: Each PDAC patient would have an average of 4.35 living FDRs. 1.32 of these living FDRs would be informed of the patient’s test results but not undergo testing themselves, and 1.03 would test positive for the mutation of interest. For lower risk mutations (ATM, BRCA2, PALB2), FDRs would only undergo screening if they test positive. For Lynch syndrome, not tested FDRs would undergo screening starting at age 65 or 70, whereas FDRs who test positive would start at 50 or 55. For STK11, the highest risk mutation, FDRs would start screening annually as soon as they are informed of the patient’s test results. The total LE gain for cascade testing of FDRs ranged from 0 (BRCA1) to 1.05 years (STK11). Conclusions: For each PDAC patient identified to have a germline genetic mutation, cascade testing of FDRs could add up to a year life expectancy for the family, in addition to the value of the germline information to the PDAC patient’s care. [Table: see text]
Outcomes in late-line systemic treatment in GISTs: Does sequence matter?
Authors: Prapassorn Thirasastr, Cissimol Joseph, Dejka M. Araujo, Robert S. Benjamin, Anthony Paul Conley, J Andrew Andrew Livingston, Joseph Aloysius Ludwig, Shreyaskumar Patel, Ravin Ratan, Vinod Ravi, Maria Alejandra Zarzour, Xiao Zhou, Neeta Somaiah
Journal: Journal of Clinical Oncology (2022)

11542 Background: Ripretinib (R) is approved for 4 th line treatment of GIST based on superior PFS and OS compared to placebo in a phase 3 study, with RR of 11.8% and PFS of 6.3 months (mo). In addition to having high potency against PDGFRA D842V, avapritinib (A) showed activity in 4 th or later lines for KIT mutated patients (pts). The RR was 17% and median duration of response was 10.2 mo from a phase 1 study. It is not known if pts receiving R benefit from A after progression or vice-versa. We retrospectively reviewed outcomes of R and A to determine if sequence affects outcomes. Methods: Pts diagnosed with GISTs and treated with both R and A at UTMDACC from Jan 2016 to Dec 2021 were included. Pts were separated into R-A (RA) or A-R sequence (AR) and outcomes were tabulated. Descriptive statistics were used to summarize characteristics and genetic profiles. Differences between RA and AR groups were calculated using Fisher’s exact. Response was evaluated using RECIST. Kaplan-Meier and Log-rank test were used to estimate and compare PFS and OS between groups. Results: Twenty pts were included in the study; 12 in RA and 8 in AR. Median age was 55 years (R:29.7-76.3). Most pts had small bowel primary (11/20, 55%) followed by stomach (4/20, 20%). All baseline characteristics and mutations were equitably distributed between RA and AR. RR of R was 17% and 14% in RA and AR groups, respectively and RR of A was 33% and 29% in RA and AR, respectively (Table). None of the pts with secondary exon 13 mutations responded to R or A. The drug administration sequence did not affect RR (p = 0.7, 0.62 in R, A). The PFS of the second drug administered, was shortened. PFS did not differ based on type of KIT mutation. Median OS from diagnosis in RA and AR groups were 121.8 (58.2-NR) and 171.3 (73.3-NR) mo, respectively and median OS from start of RA and AR was 43.9 (23.0-NR) and NR (11.5-NR) mo, respectively. Neither difference was statistically significant. Conclusions: Both R and A are efficacious in later lines of treatment, with greater benefit from the agent used first. Although, the combined PFS was numerically higher in AR compared to RA (20.5 vs 15.2 mo), the OS was not different. Currently, R is the only drug approved in the 4 th or later lines in KIT-mutated GIST. [Table: see text]
INSP-01. What to do when you cannot randomize? Leveraging Historical Data in Efficient Study Designs for Pediatric Neuro-Oncology.
Authors: Arzu Onar-Thomas
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Randomized phase III studies represent the gold standard in clinical trial design for many good reasons. They control bias and the effects of known and unknown covariates on outcomes of interest. Recent examples from Children’s Oncology Group Medulloblastoma studies have demonstrated their utility in providing insights that likely would not have been possible otherwise. However, experience with these trials also reaffirmed that large, randomized studies often take too long to keep up with the ever-changing landscape in pediatric Neuro-Oncology, and the rarity of these tumors is a significant barrier in utilizing such designs effectively. METHODS: Recent global efforts in pediatric Neuro-Oncology have led to rich, well annotated repositories that contain patient-level data. While these data suffer from the well-known limitations when used as sole comparison cohorts for ongoing studies, they also offer an opportunity to design more efficient studies in ultra-rare patient populations that trialists in pediatric neuro-oncology often face. Therefore, there is renewed effort in the statistical community in devising methodologies that can effectively utilize external data in the design of prospective studies. These approaches include incorporating external data as a supplement to a small fraction of patients randomized to standard of care arms and prospectively assessing similarity with an intent to minimize overall sample size. Others focus on patient selection methodologies from external controls with an intent to optimize matching between the retrospective and prospective cohorts to control for known covariates. Additional considerations include incorporating arms into the study that retain standard of care treatments to capture the magnitude of drift in outcome over time due to improved supportive care. CONCLUSIONS: While there are important limitations to designs based on external controls, judicious choice of design parameters and careful selection of controls could provide a viable alternative when rarity of patient populations make randomized designs infeasible.
Laparoscopic versus ultrasound guided Transversus Abdominis Plane (TAP) block for postoperative analgesia after radical prostatectomy: A randomized controlled trial
Authors: A. Civitella, F. Prata, P. Tuzzolo, L. Romei, V.G. Crimi, F. Tedesco, A. Ragusa, L. Cacciatore, N. Deanesi, A. Testa, G.P. Flammia, A. Alcini, A. Salerno, S.M. Prata, F. Esperto, R.M. Scarpa, R. Papalia
Journal: European Urology (2022)
Regional Therapy for Colorectal Cancer Liver Metastases: Which Modality and When?
Authors: Michael J. Raphael, Paul J. Karanicolas
Journal: Journal of Clinical Oncology (2022)

For patients with unresectable colorectal liver metastases (uCRLM), regional therapies leverage the unique, dual blood supply to the liver; the hepatic artery is the main blood supply for liver tumors, whereas the portal vein supplies most normal hepatic parenchyma. Infusion of cancer therapies via the hepatic artery allows selective delivery to the tumors with relative sparing of normal liver tissue and little extrahepatic exposure, thus limiting systemic side effects. There is a paucity of randomized controlled trial evidence to inform the optimal integration of regional therapies into the management of CRLM. Hepatic arterial infusion pump (HAIP) chemotherapy has a potential survival benefit when used in the adjuvant setting after resection of CRLM. HAIP chemotherapy can be safely given with contemporary systemic therapies and is associated with a high objective response and rate of conversion to resectability in patients with uCRLM. Drug-eluting beads coated with irinotecan transarterial chemoembolization is associated with high objective response rates within the liver and has a well-established safety profile in patients with uCRLM. Transarterial radioembolization achieves high rates of response within the liver but is not associated with improvements in overall survival or quality of life in the first- or second-line setting for uCRLM. The best treatment approach is the one that most aligns with a given patients' values, preferences, and philosophy of care. In the first-line setting, HAIP could be offered to motivated patients who hope to achieve conversion to resectability. After progression on chemotherapy, HAIP, transarterial chemoembolization, and transarterial radioembolization are valuable treatment options to consider for patients with liver-limited or liver-predominant CRLM who seek to optimize response rates and regional control.
LINC-20. Impact of the COVID-19 pandemic on 30-day mortality and unplanned reoperation rates for pediatric central nervous system tumors
Authors: Diana Jovett Sanchez, Sally Andrea Gaspi, Ceri Jane Talan, Ana Patricia Alcasabas, Ronnie Baticulon
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Unplanned reoperations and mortality within 30 days are important indicators when evaluating the quality of care provided by surgical systems. We reviewed these outcomes among children with primary central nervous system (CNS) tumors treated during the COVID-19 pandemic. METHODS: This is a retrospective study of all pediatric patients who underwent neurosurgery for primary CNS tumors at the Philippine General Hospital, the national university hospital, from January 1, 2020 until December 31, 2021. Their clinical presentation, perioperative course, and outcomes were analyzed. During this time, our hospital concurrently served as a COVID-19 referral center, thus, the workforce was restructured, and resources were reallocated to care for COVID-19 patients. RESULTS: A total of 92 pediatric patients with CNS tumors underwent 140 neurosurgical operations during the study period. Two-thirds of the patients were males, and mean age was 9.3 ± 5.0 years (range: 3 months to 18 years). Average preoperative length of stay was 3.9 ± 2.6 days. Tumor resection was performed in 73 patients (79%). Most common histologic diagnoses were medulloblastoma (20%) and low-grade glioma including pilocytic astrocytoma (20%). Overall, the 30-day mortality and unplanned reoperation rates were 12% and 22%, respectively. Eight patients died from brain herniation and/or tumor progression. Reasons for unplanned reoperations were postoperative hydrocephalus (20%), infection (9%), hematoma (7%), and tumor residual (3%). DISCUSSION: Worldwide, the COVID-19 pandemic has altered hospital protocols and shifted resources considerably. The observed high rates of death and reoperation are likely due to delays in seeking care leading to worse neurologic status at presentation, delays in performing essential surgery within the hospital, and shortage of health workers providing specialist care. It is important to periodically assess perioperative outcomes to improve the quality of surgical care given to children with CNS tumors, who remain a vulnerable population during the COVID-19 pandemic.
RONC-15. FEASIBILITY AND EFFECTIVENESS OF REIRRADIATION IN CHILDREN AND ADOLESCENTS WITH RELAPSED OR RESISTANT BRAIN TUMORS
Authors: Anna Campello, Anna Mussano, Stefano Vallero, Daniele Bertin, Paola Peretta, Giovanni Morana, Paola Sciortino, Federica Ricci, Luca Bertero, Franca Fagioli
Journal: Neuro-Oncology (2022)

Abstract Few reports exist about reirradiation (RT2) for recurrent brain tumors in pediatric patients.A monocentric retrospective analysis of 22 patients with reirradiated CNS neoplasms was conducted with the objective to describe clinical outcomes and toxicities associated with RT2. Median age at diagnosis and RT2 was 8.5 years and 11.5 years respectively. Primary diagnoses included ependymoma (n=7, 32%), medulloblastoma (n=5, 23%), DIPG (n=4, 18%), glioblastoma (N=2, 9%), and others (N=4, 18%). The median interval between the first radiotherapy and RT2 was 16.5 months. Two patients underwent in-field RT2 for a secondary tumor. RT2 was administered with a curative intent in 13 patients, with a palliative-only treatment in the remaining 9. Sixteen patients received brain RT2 and 3 patients spine RT2, with a median cumulative dose of 19.9 Gy and 30 Gy respectively. Three patients received combined RT2. Volumetric Modulated Arc Therapy(VMAT) was the most frequent technique used (60%). Eight patients showed neurological symptoms before RT2, 6 had clinical benefit with RT2. Among patients who were asymptomatic before RT2, 5 later showed progressive neurological symptoms (at least partly attributable to RT2). Radionecrosis was radiologically detected in 6 patients, but accompanied by symptoms only in 3. Median event-free survival (EFS) and overall survival(OS) after RT2 was 4.7 and 8.7 months respectively, similarly to previous results. One-year EFS and OS was 13% and 36% respectively. As previously reported, OS appeared to be longer for patients with &amp;gt;12 months elapsed time between first irradiation and RT2 (1-year OS=45% versus 0%, p=0.07). In our cohort RT2 appeared feasible and provided short-term disease control with tolerable short-term toxicity, while providing relief in most symptomatic patients. Larger prospective studies are needed to understand which subsets of patients may benefit from either curative or palliative reirradiation, to provide respectively a longer survival and a significantly improved symptom control.